Long-term ascorbic acid administration reverses endothelial vasomotor dysfunction in patients with coronary artery disease

Background-Loss of endothelium-derived nitric oxide (EDNO) contributes to t he clinical expression of coronary artery disease (CAD). Increased oxidativ e stress has been linked to impaired endothelial vasomotor function in athe rosclerosis, and recent studies demonstrated that short-term ascorbic acid treatment improves endothelial function. Methods and Results-In a randomized, double-blind, placebo-controlled study , we examined the effects of single-dose (2 g PO) and long-term (500 mg/d) ascorbic acid treatment on EDNO-dependent flow-mediated dilation of the bra chial artery in patients with angiographically established CAD. Flow-mediat ed dilation was examined by high-resolution vascular ultrasound at baseline , 2 hours after the single dose, and 30 days after long-term treatment in 4 6 patients with CAD. Flow-mediated dilation improved from 6.6+/-3.5% to 10. 1+/-5.2% after single-dose treatment, and the effect was sustained after lo ng-term treatment (9.0+/-3.7%), whereas flow-mediated dilation was 8.6+/-4. 7% at baseline and remained unchanged after single-dose (7.8+/-4.4%) and lo ng-term (7.9+/-4.5%) treatment with placebo (P=0.005 by repeated-measures A NOVA). Plasma ascorbic acid concentrations increased from 41.4+/-12.9 to 11 5.9+/-34.2 mu mol/L after single-dose treatment and to 95.0+/-36.1 mu mol/L after long-term treatment (P<0.001). Conclusions-In patients with CAD, long-term ascorbic acid treatment has a s ustained beneficial effect on EDNO action. Because endothelial dysfunction may contribute to the pathogenesis of cardiovascular events, this study ind icates that ascorbic acid treatment may benefit patients with CAD.